1. Field of the Invention
The invention is about a series of novel symmetric amides of 1,4-bis-substituted alkylenediamino-5,8-dihydroxyanthraquinones with various monocarboxylic acid, which exist in the human organism, as well as other monocarboxylic acids, which can be obtained from substances, which exist in the human organism. These monocarboxylic acids are, among others, those which contain a quaternary ammonium group, like for instance 3-hydroxybutyric acid-4-trimethylammoniumchloride (carnitine chloride) and acetic acid trimethylammonium chloride, an oxidation product of choline, the N-acetyl neuraminic acid, as well as monocarboxylic derivatives of various sugar molecules, for example gluconic acid or 2-amino gluconic acid.
2. Description of the Related Art
About three decades ago, the first anthracycline antibiotics were obtained through biological synthesis by fungus Streptomyces paucetius var. caesius. As described in the classical reference book by A. Goodman Gilman, L. S. Goodman, T. W. Rall, F. Murad, "Goodman Gilman's Pharmaceutical Basis of Therapeutics", 7th edition, McMillan Publishing Company, New York, 1985, pp 1283, anthracycline antibiotics and their derivatives show a very strong antitumor activity. One representative of this group is daunorubicine. It was isolated independently by both DiMarco and Dubost et al. in 1963. A very similar compound is the doxorubicine. It was first isolated in 1969 by Arcamone. Although these two compounds are very similar in structure, daunorubicine is primarily used in acute leukemias while doxorubicine is applied against a wide range of human neoplasms including solid tumors.
However both of these compounds showed also toxic effects to the organism (Goodman Gilman's Pharmaceutical Basis of Therapeutics, 7th edition, 1985), and can cause, depending on the dose applied, an often irreversible cardiomyopathia. Following the invention of the first anthracycline antibiotics, several anthracycline derivatives were prepared and tested in order to find an alternative compound with high antitumor activity, but at the same time with reduced cardiac toxicity. Mitoxantrone, a synthetically obtained compound, is one of these antitumor agents. It is an aminoanthracenedione (1,4-bis[2-(2-hydroxyethylamino)ethylamino]5,8-dihydroxyanthraquinone hydrochloride) and is used very frequently against various neoplastic developments in human organism. The U.S. Pat. No. 4,197,249 from 1980 is about a series of substituted anthraquinone derivatives, including mitoxantrone.
The scientific publications of Zee-Cheng and Cheng (R. K.-Y. Zee-Cheng, C. C. Cheng, "Antineoplastic agents. Structure-reactivity relationship study of bis (substituted aminoalkylamino) anthraquinones, Journal of Medicinal Chemistry, volume 21, year 1978, pages 291-294) and of Murdock et al. (K. C. Murdock, R. G. Child, P. F. Fabio, R. B. Angier, R. E. Wallace, F. E. Durr, R. V. Citarella, "Antitumor agents. 1. 1,4-Bis[(aminoalkyl)amino]-9,10-anthracenediones", Journal of Medicinal Chemistry, Volume 22, year 1979, pages 1024-1030) report about various compounds of this class.